{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T01:31:01Z","timestamp":1782869461883,"version":"3.54.5"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,4,25]],"date-time":"2020-04-25T00:00:00Z","timestamp":1587772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201606230252"],"award-info":[{"award-number":["201606230252"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CardioVascular Research Initiative Netherlands: an initiative with support of the Dutch Heart Foundation","award":["CVON2014-11, RECONNECT"],"award-info":[{"award-number":["CVON2014-11, RECONNECT"]}]},{"DOI":"10.13039\/100010447","name":"Deutsches Zentrum f\u00fcr Herz-Kreislaufforschung","doi-asserted-by":"publisher","award":["DZHK81Z0600207"],"award-info":[{"award-number":["DZHK81Z0600207"]}],"id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Exogenous melatonin has been reported to be beneficial in the treatment of pulmonary hypertension (PH) in animal models. Multiple mechanisms are involved, with melatonin exerting anti-oxidant and anti-inflammatory effects, as well as inducing vasodilation and cardio-protection. However, endogenous levels of melatonin in treatment-na\u00efve patients with PH and their clinical significance are still unknown. Plasma levels of endogenous melatonin were measured by liquid chromatography-tandem mass spectrometry in PH patients (n = 64, 43 pulmonary arterial hypertension (PAH) and 21 chronic thromboembolic PH (CTEPH)) and healthy controls (n = 111). Melatonin levels were higher in PH, PAH, and CTEPH patients when compared with controls (Median 118.7 (IQR 108.2\u2013139.9), 118.9 (109.3\u2013147.7), 118.3 (106.8\u2013130.1) versus 108.0 (102.3\u2013115.2) pM, respectively, p all &lt;0.001). The mortality was 26% (11\/43) in the PAH subgroup during a long-term follow-up of 42 (IQR: 32\u201358) months. Kaplan\u2013Meier analysis showed that, in the PAH subgroup, patients with melatonin levels in the 1st quartile (&lt;109.3 pM) had a worse survival than those in quartile 2\u20134 (Mean survival times were 46 (95% CI: 30\u201365) versus 68 (58\u201377) months, Log-rank, p = 0.026) with an increased hazard ratio of 3.5 (95% CI: 1.1\u201311.6, p = 0.038). Endogenous melatonin was increased in treatment-na\u00efve patients with PH, and lower levels of melatonin were associated with worse long-term survival in patient with PAH.<\/jats:p>","DOI":"10.3390\/jcm9051248","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T01:29:15Z","timestamp":1588123755000},"page":"1248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Lower Plasma Melatonin Levels Predict Worse Long-Term Survival in Pulmonary Arterial Hypertension"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4898-1907","authenticated-orcid":false,"given":"Zongye","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, 3000 CB Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0113-2801","authenticated-orcid":false,"given":"Laurie W.","family":"Geenen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2336-5099","authenticated-orcid":false,"given":"Ly","family":"Tu","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 999, H\u00f4pital Marie Lannelongue, Le Plessis-Robinson, 92350 Paris, France"},{"name":"Universit\u00e9 Paris-Saclay, School of Medicine, Le Kremlin-Bic\u00eatre, 94270 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemien E.","family":"van den Bosch","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda B.","family":"de Rijke","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, 3000 CB Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irwin K. M.","family":"Reiss","sequence":"additional","affiliation":[{"name":"Department of Pediatrics\/Neonatology, Sophia Children\u2019s Hospital, Erasmus MC, University Medical Center Rotterdam, 3000 CB Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Boersma","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands"},{"name":"Department of Clinical Epidemiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2836-2241","authenticated-orcid":false,"given":"Dirk J.","family":"Duncker","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1519-8147","authenticated-orcid":false,"given":"Karin A.","family":"Boomars","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8545-4452","authenticated-orcid":false,"given":"Christophe","family":"Guignabert","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 999, H\u00f4pital Marie Lannelongue, Le Plessis-Robinson, 92350 Paris, France"},{"name":"Universit\u00e9 Paris-Saclay, School of Medicine, Le Kremlin-Bic\u00eatre, 94270 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4852-831X","authenticated-orcid":false,"given":"Daphne","family":"Merkus","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands"},{"name":"Walter Brendel Center of Experimental Medicine (WBex), LMU Munich, 81377 Munich, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance (MHA), 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1801913","DOI":"10.1183\/13993003.01913-2018","article-title":"Haemodynamic definitions and updated clinical classification of pulmonary hypertension","volume":"53","author":"Simonneau","year":"2019","journal-title":"Eur. 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